PROJECT SUMMARY ? Overall The University of Kentucky Center for Appalachian Research in Environmental Sciences (UK-CARES) will establish an Environmental Health Sciences Core Center to enhance research capacity focused on major environmental health impacts to air and water quality that have been implicated in environmentally induced disease. This Center will provide advanced infrastructure and leading expertise, dedicated career development and mentorship, and community-engaged interactions to facilitate innovative discovery and new understandings of environmental factors in disease initiation, progression, and outcomes and their community impacts. The central hypothesis is that toxic environmental agents are contributors to the disproportionately high incidence of chronic diseases, e.g., cancers, cardiopulmonary disease, and metabolic disorders in Appalachian Kentucky and that the impacts of early exposure are especially harmful. UK-CARES draws on a strong and diverse base of environmental health science and community-engaged research to build environmental health research capacity to meet the needs of communities in three Area Development Districts in southeastern Kentucky: Big Sandy, Kentucky River, and Cumberland Valley. Center members bring notable strengths in environmental health across four Research Interest Groups: Cardiopulmonary Diseases, Metabolic Disorders, Cancer, and Child Health and Early Life Exposures. To achieve the Center?s goal, UK-CARES will: 1) establish a rich research environment and a framework for transdisciplinary leadership and integrated infrastructure to facilitate collaboration and efficient use of resources for research expansion and development of new scientific directions; 2) build research capacity in environmental health sciences by providing an outstanding intellectual environment and advanced infrastructure to support innovation and community engagement; 3) recruit new talent and facilitate career development of investigators whose research addresses critical issues in environmentally induced disease through mentorship and structured career training activities; 4) develop multi-directional and mutually beneficial communications and interactions with community residents, policymakers, and public health/healthcare professionals to identify environmental concerns of target communities as a stimulus to new research; and 5) bridge the gap between discovery of novel research findings and population-level awareness and practice via community-focused science communication training. An Integrative Health Sciences Facility Core, Analytical Core, and Community Outreach and Engagement Core are integral to this effort and will catalyze multi-directional translation across the whole spectrum of research; provide advanced analytical support in metabolomics, computational biology, analytical chemistry, biospecimen management, and bioinformatics; and bridge Center and community priorities. Complementary activities in career development of scientists who are interested in tackling challenging environmental health questions and pilot project funding will support developing research and evolving scientific directions.